The monoamine reuptake inhibitors from the class of the tricyclic antidepressants (TCAs) have been used successfully in the treatment of depression since the 1960s. The relevance of dysfunctions of the monoaminergic systems in psychiatric disorders is widely recognised on account of the pre-clinically and clinically proven antidepressant activities of TCAs, selective serotonin reuptake inhibitors (so-called SSRIs), selective noradrenaline reuptake inhibitors, mixed serotonin and noradrenaline reuptake inhibitors (so-called SNRIs), monoamineoxidase inhibitors and modulators of various serotonin and noradrenaline receptor subtypes (Berman et al., Biol Psychiatry, 2002 Mar 15; 51(6): 469-73). In addition, antidepressants are important adjuvants in the therapy of pain, especially in the case of chronic pain. However, monoamine reuptake inhibitors also induce an independent analgesic activity by activating the decreasing inhibition of spinal nociceptive signals. Successes in the treatment of urinary incontinence by the use of monoamine reuptake inhibitors have also been described (Sorbera et al., Drugs of the future, 2000, Vol 25, page 907-916). Monoamine reuptake inhibitors are additionally suitable for the treatment of anxiety, fibromyalgia, eating disorders, bulimia, hyperactivity (attention deficit hyperactivity disorder; ADHD), drug dependency, addiction and withdrawal, trichotillomania, skin diseases such as post-herpetic neuralgia and pruritus, memory disorders, cognitive disorders and Alzheimer's disease.
The therapeutic use of the previously-known antidepressants is limited by the undesirable side-effects that frequently occur. Particular mention may be made here of constipation, urinary retention, dryness of the mouth, accommodation disturbances, orthostatic hypotension with tachycardia, sedation, serotonin syndrome, sexual dysfunctions, dizziness, cognitive dysfunctions and QT lengthening including torsade de pointes. In the treatment of psychiatric disorders, a late onset of action, a high rate of relapse and an absence of action in 20-30% of patients are disadvantageous.